Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX10KKR)

• DOT Name: Neuferricin (CYB5D2)
• Synonyms: Cytochrome b5 domain-containing protein 2
• Gene Name: CYB5D2
• Related Disease:
  Neoplasm
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Non-insulin dependent diabetes
  Squamous cell carcinoma
• UniProt ID: NEUFC_HUMAN
• Pfam ID: PF00173
• Sequence:
  MLRCGGRGLLLGLAVAAAAVMAARLMGWWGPRAGFRLFIPEELSRYRGGPGDPGLYLALL
  GRVYDVSSGRRHYEPGSHYSGFAGRDASRAFVTGDCSEAGLVDDVSDLSAAEMLTLHNWL
  SFYEKNYVCVGRVTGRFYGEDGLPTPALTQVEAAITRGLEANKLQLQEKQTFPPCNAEWS
  SARGSRLWCSQKSGGVSRDWIGVPRKLYKPGAKEPRCVCVRTTGPPSGQMPDNPPHRNRG
  DLDHPNLAEYTGCPPLAITCSFPL
• Function: Heme-binding protein which promotes neuronal but not astrocyte differentiation.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[2]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neuferricin (CYB5D2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuferricin (CYB5D2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuferricin (CYB5D2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuferricin (CYB5D2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuferricin (CYB5D2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Neuferricin (CYB5D2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Neuferricin (CYB5D2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Neuferricin (CYB5D2).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Neuferricin (CYB5D2).	[12]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Neuferricin (CYB5D2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neuferricin (CYB5D2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Neuferricin (CYB5D2).	[15]

References

• [1] Downregulation of CYB5D2 is associated with breast cancer progression.Sci Rep. 2019 Apr 29;9(1):6624. doi: 10.1038/s41598-019-43006-y.
• [2] CYB5D2 displays tumor suppression activities towards cervical cancer.Biochim Biophys Acta. 2016 Apr;1862(4):556-565. doi: 10.1016/j.bbadis.2015.12.013. Epub 2015 Dec 12.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [13] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.